To assess the natural history of Human papillamavirus (HPV) infections in uterine cervix (fat, inverted and papillomatous condylomas) and their associations with cervical intraepithelial neoplasia (CIN) and cervical cancer, a long-term prospective follow-up study was started at our clinic in October 1981. At this writing, a total of 418 women have been followed-up for a mean of 20 15 (M SD) months, either by cervical punch biospy or Papanicolaou (PAP) smears, repeated at 6-month intervals. On each attendance at the Clinic, the patient is subjected to colposcopy. To evaluate the role accompanying cervical infections, cervical swabs (for isolation of Chlamydia trachomatis and HSV), and by serum samples for viral (HPV, HSV, CMV) serology. PAP smears and punch biopsies are analysed for cytopathic changes of HPV (koilocytosis, dyskeratosis), and for concomitant CIN, and the biopsies also for HPV particles on transmission electron microscopy (TEM). Expression of HPV structural proteins is demonstrated with indirect immunoperoxidase (IP-PAP) technique applied on paraffin sections. In fresh biopsy samples (on frozen sections), the immunocampetent cells within the in situ inflammatory infiltrate are phenotypically characterized using monoclonal antibodies (McAB) to define T cell subsets, NK (natural killer) cells and Langerhans cells. Spot and in situ hybridization as well as Sothern blot are used to detect and analyse HPV DNA with cloned HPV type 6, 11, 16 and 18 DNA as probes. Biopsy specimens will also be tested for amplification of the major cellular oncogenes (c-onc). To assess the factors with influence on transmission of cervical HPV infections, all patients are requested for their sexual and smoking habits by a detailed questionnaire. The incidence and prevalence of cervical HPV infections in unselected Finnish female population are determined by an epidemiological study, utilizing the mass-screening programme of the Finnish Cancer Society. The preliminary results suggest that cervical HPV infections seem to be capable of progressing event into CIS, and thus present with the natural history comparable to that of classical CIN.